BETA-CAROTENE INHIBITS ATHEROSCLEROSIS IN HYPERCHOLESTEROLEMIC RABBITS

Oxidatively damaged LDL may be of central importance in atherogenesis. Epidemiological evidence suggests that high risk for atherosclerotic vascular disease, raising the possibility that lipid-soluble antioxida nts slow vascular disease by protecting LDL from oxidation. To test th is hypothesis, we fed male New Zealand White rabbits a high-cholestero l diet or the same diet supplemented with either 1% probucol, 0.01% vi tamin E, 0.01% all-trans beta-carotene, or 0.01% 9-cis beta-carotene; then we assessed both the susceptibility of LDL to oxidation ex vivo a nd the extent of aortic atherasclerosis. As in earlier studies, probuc ol protected LDL from oxidation and inhibited lesion formation. In con trast, vitamin E modestly inhibited LDL oxidation but did not prevent atherosclerosis. While beta-carotene had no effect on LDL oxidation ex vivo, the all-trans isomer inhibited lesion formation to the same deg ree as probucol. Moreover, all-trans beta-carotene was undetectable in LDL isolated from rabbits fed the compound, although tissue levels of retinyl palmitate were increased. The effect of all-trans beta-carote ne on atherogenesis can thus be separated from the resistance of LDL t o oxidation, indicating that other mechanisms may account for the abil ity of this compound to prevent vascular disease, Our results suggest that metabolites derived from all-trans beta-carotene inhibit atherosc lerosis in hypercholesterolemic rabbits, possibly via stereospecific i nteractions with retinoic acid receptors in the artery wall.